Background:Recognizing sport-related concussion(SRC)is challenging and relies heavily on subjective symptom reports.An objective,biological marker could improve recognition and understanding of SRC.There is emerging e...Background:Recognizing sport-related concussion(SRC)is challenging and relies heavily on subjective symptom reports.An objective,biological marker could improve recognition and understanding of SRC.There is emerging evidence that salivary micro-ribonucleic acids(miRNAs)may serve as biomarkers of concussion;however,it remains unclear whether concussion-related miRNAs are impacted by exercise.We sought to determine whether40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports.Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.Methods:This case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites.Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing.Within-subjects testing was used to identify and exclude miRNAs that changed with either(a)a single episode of exercise(166 samples from 83 individuals)or(b)season-long participation in contact sports(212 samples from 106 individuals).The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression(172 samples from 75 concussed and 97 non-concussed individuals).Results:Two miRNAs(miR-532-5p and miR-182-5p)decreased(adjusted p<0.05)after a single episode of exercise,and 1 miRNA(miR-4510)increased only after contact sports participation.Twenty-three miRNAs changed at the end of a contact sports season.Two of these miRNAs(miR-26b-3p and miR-29c-3p)were associated(R>0.50;adjusted p<0.05)with the number of head impacts sustained in a single football practice.Among the 15 miRNAs not confounded by exercise or season-long contact sports participation,11 demonstrated a significant difference(adjusted p<0.05)between concussed and non-concussed participants,and 6 displayed moderate ability(area under curve>0.70)to identify concussion.A single ratio(miR-27a-5p/miR-30a-3p)displayed the highest accuracy(AUC=0.810,sensitivity=82.4%,specificity=73.3%)for differentiating concussed and non-concussed participants.Accuracy did not differ between participants with SRC and non-SRC(z=0.5,p=0.60).Conclusion:Salivary miRNA levels may accurately identify SRC when not confounded by exercise.Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive,sideline adjunct for SRC assessment.展开更多
Maintenance with methadone is standard treatment for opioid-addicted patients, including pregnant women. Cellular effects of methadone exposure during development are investigated by using an avian model, which is fre...Maintenance with methadone is standard treatment for opioid-addicted patients, including pregnant women. Cellular effects of methadone exposure during development are investigated by using an avian model, which is free of confounding maternal variables. In the first study, which explored dose by duration interactions, methadone was administered at one of two doses (0.458 mg/kg or 1.75 mg/kg) for one of three durations of exposure: late in development (Incubation Days 12 to 19), middle to late (Days 9 to 19), or early to late (Days 5 to 19). In the second study, 1.00 mg/kg of methadone was administered from days 8 to 18 and compared with controls (0.00 mg/kg). Brain tissue and blood samples were harvested for all dose conditions from the two studies. Increased methadone exposure was associated with subependymal anomalies, subependymal hemorrhaging, edema, monocytic infiltration, an increase in disintegrating red blood cells, an increase in white blood cells, and a decrease in neurons. Significant differences in variance for cell counts by condition were observed. Exposed specimens had significantly more thrombocytes (t = - 2.66, p < 0.05). The anomalies suggest that methadone exposure may be harmful to develop organisms at the cellular level.展开更多
基金supported by a sponsored research agreement between Quadrant Biosciences and the Penn State College of Medicine to ACLsupported by the National Center for Advancing Translational Sciences(Grant KL2 TR002015,Grant UL1 TR002014)。
文摘Background:Recognizing sport-related concussion(SRC)is challenging and relies heavily on subjective symptom reports.An objective,biological marker could improve recognition and understanding of SRC.There is emerging evidence that salivary micro-ribonucleic acids(miRNAs)may serve as biomarkers of concussion;however,it remains unclear whether concussion-related miRNAs are impacted by exercise.We sought to determine whether40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports.Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.Methods:This case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites.Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing.Within-subjects testing was used to identify and exclude miRNAs that changed with either(a)a single episode of exercise(166 samples from 83 individuals)or(b)season-long participation in contact sports(212 samples from 106 individuals).The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression(172 samples from 75 concussed and 97 non-concussed individuals).Results:Two miRNAs(miR-532-5p and miR-182-5p)decreased(adjusted p<0.05)after a single episode of exercise,and 1 miRNA(miR-4510)increased only after contact sports participation.Twenty-three miRNAs changed at the end of a contact sports season.Two of these miRNAs(miR-26b-3p and miR-29c-3p)were associated(R>0.50;adjusted p<0.05)with the number of head impacts sustained in a single football practice.Among the 15 miRNAs not confounded by exercise or season-long contact sports participation,11 demonstrated a significant difference(adjusted p<0.05)between concussed and non-concussed participants,and 6 displayed moderate ability(area under curve>0.70)to identify concussion.A single ratio(miR-27a-5p/miR-30a-3p)displayed the highest accuracy(AUC=0.810,sensitivity=82.4%,specificity=73.3%)for differentiating concussed and non-concussed participants.Accuracy did not differ between participants with SRC and non-SRC(z=0.5,p=0.60).Conclusion:Salivary miRNA levels may accurately identify SRC when not confounded by exercise.Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive,sideline adjunct for SRC assessment.
文摘Maintenance with methadone is standard treatment for opioid-addicted patients, including pregnant women. Cellular effects of methadone exposure during development are investigated by using an avian model, which is free of confounding maternal variables. In the first study, which explored dose by duration interactions, methadone was administered at one of two doses (0.458 mg/kg or 1.75 mg/kg) for one of three durations of exposure: late in development (Incubation Days 12 to 19), middle to late (Days 9 to 19), or early to late (Days 5 to 19). In the second study, 1.00 mg/kg of methadone was administered from days 8 to 18 and compared with controls (0.00 mg/kg). Brain tissue and blood samples were harvested for all dose conditions from the two studies. Increased methadone exposure was associated with subependymal anomalies, subependymal hemorrhaging, edema, monocytic infiltration, an increase in disintegrating red blood cells, an increase in white blood cells, and a decrease in neurons. Significant differences in variance for cell counts by condition were observed. Exposed specimens had significantly more thrombocytes (t = - 2.66, p < 0.05). The anomalies suggest that methadone exposure may be harmful to develop organisms at the cellular level.
